USPSTF: Most Vitamin, Supplement Data Still ‘Inconclusive’ on CVD Benefits

The United States Preventive Services Task Force (USPSTF) has released updated guidance regarding vitamin and mineral supplements for the prevention of cardiovascular disease and cancer, looking anew at the topic with more than three times as many studies as before. Still, due to the lack of evidence on both benefits and harms, they continue to recommend against the use of beta carotene and vitamin E but otherwise offer no advice for the use of supplements.

That means that nothing is substantially different in the USPSTF’s most-recent recommendations compared with the last document in 2014, which was based on 26 studies. The latest statement, published in the June 21, 2022, issue of JAMA, includes evidence from a total of 84 studies, including 52 new ones like the large—and neutral—VITAL trial.

Even with so many additional studies, however, the task force concluded that the current evidence is “insufficient” (I statement) to assess the balance of benefits and harms of the use of multivitamin supplements, single supplements, or most paired supplements for the prevention of cardiovascular disease or cancer. On the other hand, both beta carotene and vitamin E supplements for the prevention of cardiovascular disease or cancer are specifically singled out with a D recommendation (do not use) because of a possible increased risk of mortality, cardiovascular mortality, and lung cancer.

The vitamin and supplement market remains a multibillion dollar industry in the United States, with more than half of US adults saying they regularly use at least one dietary supplement, with the aim of improving “overall health and wellness” and to fill nutrient gaps, the USPSTF recommendations note. The anti-inflammatory and antioxidative properties of many supplements has “served as a rationale for proposing dietary supplements as a means to prevent both cardiovascular disease and cancer,” the authors say, despite little evidence to support this.

‘Teachable Moments’

Speaking with TCTMD, Michael Barry, MD (Massachusetts General Hospital, Boston, MA), vice chair of the USPSTF, emphasized that an I statement “isn't saying, ‘Don't do it’ or ‘Do it.’ It's saying, ‘We don't have enough evidence to go in one direction another.’”

For heart disease in particular, he added, “there are many effective interventions, including a healthy diet, exercise, maintaining a healthy weight, use of statin therapy in the right groups of people, controlling blood pressure, et cetera. We want to be sure that people don't think that taking a vitamin is a replacement for those proven effective practices for reducing cardiovascular disease events. So, rather than see this as a negative, we think maybe it's a good time to emphasize the positive for all the things people can do to reduce their heart disease risk.”

Barry did stress the importance of folic acid supplementation in persons planning to become pregnant, with the aim of preventing neural tube defects in their babies. “Cardiologists see people like that,” he said. “That is a recommendation that we think is important for all clinicians to emphasize.”

Erin Michos, MD (Johns Hopkins University School of Medicine, Baltimore, MD), who commented on the statement for TCTMD, pointed out that the costly habit of taking regular vitamins and supplements is usually linked to a general motivation to want to be healthy.

“I think most people are unaware that the data are really weak or essentially null, frankly, in demonstrating any kind of benefit for cardiovascular disease and cancer for supplement use,” Michos said. “When my patients come in and they have like 15 different bottles of supplements and I ask about them, they say, ‘Well, I want to take a natural approach.’ But [I tell them], ‘There's nothing more natural than following a healthy diet and lifestyle.’”

She said she likes to use these occasions as “teachable moments,” but also advised cardiologists to be on the lookout for potential drug-drug interactions, like the heightened bleeding risk associated with omega-3’s or ginkgo biloba when paired with direct oral anticoagulants or dual antiplatelet therapy. “Many patients are not aware, because they bought this thing in a health food store and they think it's completely benign,” she said. “It's a good opportunity to figure out why they are choosing to take that particular supplement, and I use it for a conversation to talk to them about healthy lifestyle, which is the foundation for all prevention, even for patients who require medications like statins.”

With prior research showing that patients often don’t disclose which supplements they are taking to their physicians, Michos also advised cardiologists to explicitly ask about them. “We just ask what medications they're taking, but specifically ask them about supplements because they can interact with many common prescription medications, including ones that we use in cardiology.”

In an editorial accompanying the statement, Jenny Jia, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), and colleagues agree that clinicians should focus more on lifestyle counseling to prevent chronic disease through evidence-based approaches. However, they write, “healthy eating can be a challenge when the US industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.”

The editorialists advocate for more screening for food insecurity at the patient level, increased support for organizations promoting health at the community level, and better policies that increase access to healthy foods and environments for physical activity at a government level.

More Research Necessary?

Michos agreed that these changes—taking steps to ease the path towards a healthier lifestyle—are where future priorities should lie, not in spending more money on trials of vitamins and supplements. “If there is any cardiovascular benefit, it's going to be really modest,” she said. “You would have to enroll huge numbers of patients that follow them for a very long time, and I just think it's not worth investing in more vitamin and supplement trials. It's been studied. It's been done. There's no benefit that's been demonstrated. Rather, I think we need to focus on how we can better deliver other aspects of prevention like how to implement healthy diet and lifestyle.”

Also, she continued, “a whole other issue is how to optimize delivery of other evidence-based, pharmacological prevention therapy for patients at high risk. We know statin therapy continues to be underutilized and patients undertreated and not at LDL goals and blood pressure is still not adequately controlled and the diabetes is rising and obesity skyrocketing. And so that's the kind of studies I think that we need, not more money dumped into supplement studies.”

Barry, on the other hand, argued that there is still room for more research in this space. In particular, he said he’d like to see, “studies that follow people for much longer periods of time than the average in our existing studies just to see if there is evidence of delayed benefits or harms for that matter.” Moreover, he said more research is warranted “in different populations to see if there are any special effects of vitamin and mineral supplements in key parts of our population.”

In an email, Elizabeth A. O’Connor, PhD (Kaiser Permanente Northwest, Portland, OR), who served as lead author on the evidence report that the USPSTF used to form its statement, told TCTMD she would like to see long-term follow-up on the COSMOS trial of multivitamin use since it’s “large enough” to look into potential differences by race and weight. “This is really the best evidence for multivitamin use, but at this point only has 3.6 years of follow-up [which is] really too short of a time-frame to have much of an impact on CVD outcomes among a general population,” she said.

Additionally, O’Connor said she is “intrigued by some of the findings for vitamin E on CVD mortality. For the most part vitamin E demonstrated no benefit, certainly no benefit for all-cause mortality or cancer. But there were several studies with some findings hinting at a possible benefit for some CVD outcomes. For this reason, I think longer follow-up for the SELECT and PPP studies would be valuable.”